Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2014 Feb 15;24(4):1094-7. doi: 10.1016/j.bmcl.2014.01.010. Epub 2014 Jan 11.

Synthesis of 2',3',4'-trihydroxyflavone (2-D08), an inhibitor of protein sumoylation.

Author information

1
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, 376 Boyles St., Frederick, MD 21702, USA.
2
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, 376 Boyles St., Frederick, MD 21702, USA. Electronic address: schneeklothjs@mail.nih.gov.

Abstract

Protein sumoylation is a dynamic posttranslational modification involved in diverse biological processes during cellular homeostasis and development. Recently sumoylation has been shown to play a critical role in cancer, although to date there are few small molecule probes available to inhibit enzymes involved in the SUMO conjugation process. As part of a program to identify and study inhibitors of sumoylation we recently reported the discovery that 2',3',4'-trihydroxyflavone (2-D08) is a cell permeable, mechanistically unique inhibitor of protein sumoylation. The work reported herein describes an efficient synthesis of 2-D08 as well as a structurally related but inactive isomer. We also report an unanticipated Wessely-Moser rearrangement that occurs under vigorous methyl ether deprotection conditions. This rearrangement likely gave rise to 2-D08 during a deprotection step, resulting in 2-D08 appearing as a contaminant in a screening well from a commercial supplier.

KEYWORDS:

Flavone; Inhibitor; SUMO; Synthesis

PMID:
24468414
PMCID:
PMC3970184
DOI:
10.1016/j.bmcl.2014.01.010
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center